InterPro domain: IPR036880

The majority of the sequences having this domain belong to the MEROPS inhibitor family I2, clan IB; the Kunitz/bovine pancreatic trypsin inhibitor family, they inhibit proteases of the S1 family [ 1 ] and are restricted to the metazoa with a single exception: Amsacta moorei entomopoxvirus. They are short (~50 residue)alpha/beta proteins with few secondary structures. The fold is constrainedby 3 disulphide bonds. The type example for this family is aprotinin (bovine pancreatic trypsin inhibitor) [ 2 ] (or basic protease inhibitor), but the family includes numerous other members[ 3 , 4 , 5 , 6 ], such as snake venom basic protease; mammalian inter-alpha-trypsininhibitors; trypstatin, a rodent mast cell inhibitor of trypsin; a domainfound in an alternatively-spliced form of Alzheimer's amyloid beta-protein;domains at the C-termini of the alpha(1) and alpha(3) chains of type VIIand type VI collagens; and tissue factor pathway inhibitor precursor.

The pancreatic trypsin inhibitor (Kunitz) family [ 7 , 8 , 8 ] is one of thenumerous families of serine proteinase inhibitors. The basic structure ofsuch a type of inhibitor is shown in the following schematic representation:

 +-----------------------+ | +--------+ | | | **|******* | xxCxxC#xxxCxxxCxxxxxxCxxxxCxx | | +----------+ {------50 residues------}'C': conserved cysteine involved in a disulfide bond.'#': active site residue.'*': position of the pattern.

1. Evolutionary families of peptidase inhibitors. Biochem. J. 378, 705-16
2. Crystal structure of a Y35G mutant of bovine pancreatic trypsin inhibitor. J. Mol. Biol. 220, 757-70
3. Inter-alpha-trypsin inhibitor: emergence of a family within the Kunitz-type protease inhibitor superfamily. Trends Biochem. Sci. 15, 435-9
4. Evolutionary origin of a Kunitz-type trypsin inhibitor domain inserted in the amyloid beta precursor protein of Alzheimer's disease. J. Mol. Evol. 34, 536-43
5. Molecular cloning, expression, and partial characterization of a second human tissue-factor-pathway inhibitor. Proc. Natl. Acad. Sci. U.S.A. 91, 3353-7
6. Amino acid sequence of a protease inhibitor isolated from Sarcophaga bullata determined by mass spectrometry. Protein Sci. 1, 278-88
7. Protein inhibitors of proteinases. Annu. Rev. Biochem. 49, 593-626